The present invention relates to a series of novel compounds which have been found to inhibit cholesterol biosynthesis and which can thus be used in the treatment and prevention of disorders arising from high levels of cholesterol in the body. The invention also provides processes for preparing these compounds.
Hyperlipaemia, especially hypercholesteraemia, is known to be one of the main causes of cardiopathy, such as cardiac infarction or arteriosclerosis. As a result, considerable research has been carried out in an effort to discover compounds capable of reducing lipid, and especially cholesterol, levels in the blood. A group of compounds of this type is disclosed in U.S. Pat. No. 3,983,140 and was isolated from the culture broth obtained by cultivating microorganisms of the genus Penicillium; this group of compounds is collectively designated ML-236. U.S. patent applications Ser. No. 121,515, filed Feb. 14, 1980, and No. 137,821, filed Apr. 4, 1980, which issued as U.S. Pat. No. 4,323,648 on Apr. 6, 1982, disclosed a structurally similar compound designated Monacolin K or MB-530B, and certain salts and esters of MB-530B are disclosed in U.S. patent application Ser. No. 172,231, filed July 25, 1980. MB-530B and its salts may be prepared by cultivating microorganisms of the genus Monascus, especially, but not exclusively, strains of Monascus ruber. Another compound of the MB-530 group, designated MB-530A, as well as other compounds relating to the ML-236 and MB-530 groups are disclosed in co-pending Application Ser. No. 247,875 filed Mar. 30, 1981 entitled "Inhibitors of Cholesterol Biosynthesis, their Preparation and Use" and Application Ser. No. 251,733 filed Apr. 7, 1981 entitled "Compounds which Inhibit Cholesterol Biosynthesis, and their Preparation" to A. Sato et al..
We have now discovered a series of compounds related to these prior compounds which also have valuable inhibitory activity against the biosynthesis of cholesterol.